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Trefoil Factor 1 (TFF1) Expression in Intestinal Neuroendocrine Cells in Necrotising Enterocolitis

Presented at the Neonatal Society 2013 Autumn Meeting.

Vieten D1, Corfield A, Ramani P, Spicer R

Department of Paediatric Surgery, Bristol Royal Hospital for Children, Bristol, UK
Mucin Research Group, Bristol University, Bristol, UK

Background: Trefoil peptides play a key role in epithelial restitution and repair. TFF1 is thought to be part of a regulatory system that modulates mucosal structure and function and may be involved in regulation of secretion of other protective proteins in the intestinal mucosa. This study examined the expression of TFF1 in intestinal mucosal cells to assess the potential role as a modulator of epithelial regeneration and secretion of mucosal barrier proteins in necrotising enterocolitis and normal neonatal controls.

Methods: Parents of neonates up to 44 weeks gestation undergoing bowel resection were approached for consent. Samples from resection specimens were fixed in formalin and embedded in paraffin blocks. TFF1 protein localisation was determined by immunohistochemistry. Neuroendocrine cells were highlighted by staining adjacent sections for chromogranin A. For chromogranin A and TFF1 co-localisation two-layer immunohistochemistry was performed with fluorogenic signals.

Results: 50 bowel samples (28 with NEC (18 acute, 10 recovery) and 22 controls) were analysed. There was no TFF1 expression in normal controls. There was occasional TFF1 staining seen in goblet and neuroendocrine cells in 50% of NEC patients. 100% of the recovering patients had neuroendocrine cell hyperplasia and strong staining for TFF1 protein localised to these cells. Although the TFF1 acute phase response was mostly lost in the NEC bowel samples examined compared to reports of adult inflammatory bowel disease, expression in neuroendocrine cells in the recovery phase was marked.

Conclusion: TFF1-3 up-regulation in response to gut mucosal injury is linked with roles in epithelial cell migration and protection against apoptosis. The secretion of the same protein from goblet cells and neuroendocrine cells is unusual and indicates a potentially important role for TFF1 in the secretory process of mucus and neuroendocrine regulatory peptides that are essential for mucosal protection and repair in necrotising enterocolitis.

Corresponding author: danielav@doctors.org.uk

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